Vicious cycle between myeloma cell binding to bone marrow stromal cells via VLA-4-VCAM-1 adhesion and macrophage inflammatory protein-1α and MIP-1β production
Vicious cycle between myeloma cell binding to bone marrow stromal cells via VLA-4-VCAM-1 adhesion and macrophage inflammatory protein-1α and MIP-1β production
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DOI：
10.1007/s00774-008-0012-z
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发表时间：
2009-01-01
影响因子：
3.3
通讯作者：
Matsumoto, Toshio
中科院分区：
文献类型：
--
作者：
Abe, Masahiro;Hiura, Kenji;Matsumoto, Toshio
多发性骨髓瘤（MM）细胞通过极晚期抗原（VLA）-4和血管细胞粘附分子（VCAM）-1相互作用粘附于基质细胞，导致MM细胞分泌破骨细胞生成活性增强。我们已经报道了MM细胞衍生的巨噬细胞炎性蛋白（MIP）-1 α和MIP-1 β负责MM中的大多数破骨细胞生成活性。因此，粘附介导的破骨细胞生成可能是通过VLA-4-VCAM-1相互作用增强MIP-1的产生而引起的。本研究旨在阐明MM细胞来源的MIP-1是否在VLA-4-VCAM-1粘附介导的破骨细胞生成中发挥作用。MM细胞与VCAM-1的粘附上调了MM细胞的MIP-1 α和MIP-1 β的产生，并增强了MM细胞的破骨细胞生成活性。阻断MIP-1 α和MIP-1 β的作用不仅可以消除破骨细胞生成活性，还可以抑制MM细胞与VCAM-1的自发粘附。这些结果表明，MM细胞与VCAM-1的粘附上调了MM细胞的MIP-1产生，从而导致破骨细胞生成的增强。此外，结果表明，MIP-1产生的增加通过刺激VLA-4-VCAM-1粘附进一步增强MM细胞与基质细胞的结合，在MM细胞与基质细胞的粘附和MIP-1产生之间形成“恶性循环”，这是通过VLA-4-VCAM-1相互作用实现的。
Multiple myeloma (MM) cell adhesion to stromal cells via very late antigen (VLA)-4 and vascular cell adhesion molecule (VCAM)-1 interaction causes enhanced secretion of osteoclastogenic activity by MM cells. We have reported that MM cell-derived macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta are responsible for most of the osteoclastogenic activity in MM. Thus, adhesion-mediated osteoclastogenesis may be caused by enhanced production of MIP-1 via VLA-4-VCAM-1 interaction. The present study was undertaken to clarify whether MM cell-derived MIP-1 plays a role in VLA-4-VCAM-1 adhesion-mediated osteoclastogenesis. Adhesion of MM cells to VCAM-1 upregulated MIP-1 alpha and MIP-1 beta production from MM cells and enhanced production of osteoclastogenic activity by MM cells. Blockade of MIP-1 alpha and MIP-1 beta actions not only abrogated elaboration of osteoclastogenic activity, but also suppressed spontaneous MM cell adhesion to VCAM-1. These results demonstrate that MM cell adhesion to VCAM-1 upregulates MIP-1 production by MM cells to cause enhancement of osteoclastogenesis. In addition, the results suggest that the increased production of MIP-1 further enhances MM cell binding to stromal cells via stimulation of VLA-4-VCAM-1 adhesion, forming a "vicious cycle" between MM cell adhesion to stromal cells and MIP-1 production via VLA-4-VCAM-1 interaction.